Graham L. Hill

Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients

It is current clinical practice to give intravenous nutrition (IVN) to critically ill postoperative septic intensive care patients to prevent loss of body protein, although it has not hitherto been possible to confirm this by direct measurement of body composition. Using a neutron activation analysis facility adapted to provide an intensive care environment and tritiated water dilution we directly measured total body water, protein and fat before and after 10 days of IVN (mean daily non-protein energy and amino acid intakes 2,750 kcal and 127 gm) in eight adult intensive care patients. All patients had recovered from the septic shock syndrome but were still ventilator dependent at the start of IVN. Six patients survived to leave hospital. As a group, the patients lost 12.5% of body protein (mean loss 1.5 +/- SE 0.3 kg; p = 0.001) despite a gain in fat (mean 2.2 +/- 0.8 kg; p = 0.026). There were, in addition, large losses of body water in most patients (mean, 6.8 +/- 2.6 kg; p = 0.036). We conclude that substantial losses of body protein occur in critically ill septic patients despite aggressive nutritional support and that further research is urgently required on the fate of infused substrates and the efficacy of alternative nutritional therapies.

Weight loss with physiologic impairment. A basic indicator of surgical risk.

It is a long held belief that weight loss is a basic indicator of surgical risk. Many experienced surgeons, however, think otherwise. We have investigated the proposition that weight loss is a risk factor for postoperative complications but only when associated with clinically obvious physiologic impairment. Before major surgery, 102 patients had a careful history taken to ascertain if there had been recent weight loss and a reduction in the capacity for activity. Physical examination included assessment of mood, skeletal muscle function, respiratory muscle function, and wound healing. Plasma albumin was also measured. Using this information the patients were placed into one of three groups. Group I (N = 43) were normal, group II (N = 17) had weight loss > 10% but no clinical evidence of physiologic impairment, and group III (N = 42) had weight loss > 10% with clear evidence of dysfunction of two or more organ systems. The patients in group III had significantly more postoperative complications (p < 0.05). They also had more septic complications (p < 0.02) including a higher incidence of pneumonia (p < 0.05) and a longer hospital stay (p < 0.05) than patients in each of the other two groups. Objective measurements of body stores of protein and liver, and psychologic, respiratory, and skeletal muscle function, confirmed the validity of the clinical classification into the risk groups. The results demonstrate that weight loss is a basic indicator of surgical risk in modern practice providing it is associated with clinically obvious impairment of organ function. They suggest that adequate body protein stores are necessary for normal body function and for minimizing the risks of surgery.

Risk factors for postoperative pneumonia. The importance of protein depletion.

Pulmonary complications remain the most important cause of postoperative morbidity and mortality. The many advances of modern surgical care over the last 30 years have not appreciably altered the incidence of these complications. Many risk factors have been shown to contribute to this problem, but no studies have examined the impact of preoperative protein depletion on respiratory function and related this to the development of postoperative pulmonary complications. 80 patients (42 men, 38 women, median age of 64 years, with a range of 15–91 years) awaiting major elective gastrointestinal (G.I.) surgery were divided into two categories on the basis of a direct measurement of protein depletion: nonprotein-depleted patients (n = 41, mean protein loss, 2% ± 1.7 SEM) and protein-depleted patients (n = 39, mean protein loss, 36% ± 3.5 SEM). There was no significant difference between these two categories in regard to age, height, sex, surgical diagnosis, the presence of chronic lung disease, smoking, pro ortion of upper abdominal incisions, degree of obesity, the duration of anesthesia, and the use of prophylactic antibiotics and physiotherapy. There was a significant difference between these two categories of patients in regard to respiratory muscle strength (p <.025), vital capacity (p <.05), and peak expiratory flow rate (p <.005). Pneumonia developed in a significantly higher proportion of protein-depleted patients with atelectasis (p <.05), and their stay in the hospital after surgery was longer (p <.05). These data show that protein depletion is associated with an impairment of respiratory function, and is in itself a significant risk factor in the development of postoperative pneumonia.

Effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing

Thirty-two patients undergoing bowel resection were randomized to receive either immediate postoperative nasojejunal feeding with full strength Osmolite solution for 56 hours (n = 16) or routine postoperative hypocaloric fluids and gradual reintroduction of diet (n = 16). Body composition changes were measured at 14 days after operation with in vivo neutron activation analysis, the wound healing response by subcutaneous implantation of Gortex tubes, and muscle function by grip strength, maximum ventilatory volume, and stimulation of the ulnar nerve at the wrist. Postoperative fatigue up to 3 months after operation was assessed using a 10-point analogue. Successful immediate enteral nutrition was established in 12 of the 16 patients. Enterally fed patients had a mean daily caloric intake of 1179 +/- 388 kcal/d (mean +/- SD) over the first 4 postoperative days compared with 382 +/- 71 kcal/d for the controls (p less than 0.0001). The amount of hydroxyproline accumulating in the Gortex tubes was also significantly greater (2.5 +/- 1.1 nmol/g tube vs 1.5 +/- 0.8 nmol/g tube; p less than 0.02). However, the amount and composition of the weight lost was not significantly different. Muscle function was not preserved, and postoperative fatigue occurred to an equal extent in both groups. Complications were similar in both groups, except for a preponderance of bowel obstructions in the controls. The time to passage of first flatus and first bowel motion, although shorter in the fed group, did not reach significance (p = 0.07). We conclude that immediate enteral nutrition is feasible and results in an improved wound healing response.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired wound healing in surgical patients with varying degrees of malnutrition.

The relationship between nutritional state and wound healing was examined in 66 adult surgical patients. Wound-healing response was assessed by measuring the collagen content (hydroxyproline) of fine tubes of Gore-tex inserted subcutaneously along standardized needle track arm wounds. After a period of 7 days, the tubes were removed and it was found that there was a higher hydroxyproline content in the tubing of 36 normally nourished patients than there was in the tubing of 21 patients with mild protein energy malnutrition (p less than 0.01) and 9 patients with moderate to severe protein energy malnutrition (p less than 0.01). There was no difference in the wound-healing response between the two latter groups of patients who had significantly different degrees of malnutrition. The results suggest that a definite abnormality in the wound-healing response exists in malnourished surgical patients, but it occurs earlier in the course of the illness than previously supposed.

Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis.

OBJECTIVE To quantify the sequential changes in metabolic response occurring in patients with severe sepsis after the onset of peritonitis. SUMMARY BACKGROUND DATA Understanding the changes in energy expenditure and body composition is essential for the optimal management of severely septic patients; however, they have not been quantified in the context of modern surgical care. METHODS Twelve patients with severe sepsis secondary to peritonitis (median APACHE II score = 21.5) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and 5, 10, and 21 days later. Sequential measurements of acute-phase proteins and cytokine responses were also made. RESULTS Resting energy expenditure rose to 49% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.25 x resting energy expenditure. Body fat was oxidized when energy intake was insufficient to achieve energy balance. There was a positive fluid balance of 12.5 1 over the first 2 days after onset of sepsis; thereafter, body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. During the 21 -day study period, there was a loss of 1.21 kg (13%) of total body protein. During the first 10 days, 67% of the protein lost came from skeletal muscle, but after this time it was predominantly from viscera. Intracellular potassium levels were low but did not deteriorate further after hemodynamic stability had been reached. There was a reprioritization of hepatic protein synthesis that was obligatory and independent of changes in total body protein. The cytokine responses demonstrated the complexity, redundancy, and overlap of mediators. CONCLUSIONS The period of hypermetabolism in severely septic patients is similar to that previously described, but the fluid changes are larger and the protein loss is greater. Protein loss early on is predominantly from muscle, thereafter from viscera. Fat loss can be prevented and cell function preserved once hemodynamic stability is achieved.

Optimal protein requirements during the first 2 weeks after the onset of critical illness.

OBJECTIVE To obtain optimal protein requirements in critically ill sepsis or trauma patients during the first 2 wks after admission to the intensive care unit. DESIGN Retrospective study. SETTING Department of critical care medicine at a teaching hospital. PATIENTS Immediate posttrauma patients or severely septic patients. INTERVENTIONS In vivo neutron activation analysis was used to measure changes in total body protein over a 10-day period which began as soon as the patients were hemodynamically stable. The patients (trauma, n=18; sepsis, n=5) were divided into three groups according to the average daily protein intakes. Because the patients were overhydrated (approximately 10 L) and had variable amounts of body fat, the protein intakes were indexed to normally hydrated (corrected) fat-free mass (FFMc): Groups A, B, and C received an average of 1.1, 1.5, and 1.9 g/kg FFMc/day protein, respectively. MEASUREMENTS AND MAIN RESULTS Overall, the average loss of total body protein was 1.2=0.7 (SD) kg. Changes in total body protein were significantly (p=.011) different between the three groups. The loss of body protein was significantly more in group A compared with groups B (p=.013) and C (p=.023). When the protein intake was increased from 1.1 g/kg FFMc/day to 1.5 g/kg FFMc/day, protein loss was halved. Further increase in protein intake up to 1.9 g/kg FFMc/day resulted in no further improvement. An intake of 1.5 g/kg FFMc/day was equivalent to 1.0 g/day/kg of body weight measured at the beginning of the study. CONCLUSIONS Current recommended protein requirements of 1.2 to 2.0 g/kg of body weight/day are excessive if they are indexed to the body weight measured soon after the onset of critical illness. Because individual patients have varying degrees of overhydration early in the illness onset, we suggest that the intensivist should obtain information on preillness body weight and prescribe 1.2g of protein/kg body weight/day. If information is not available, 1.0g of protein/day/kg of measured body weight will give a fair approximation to optimal protein requirements.

Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma.

BACKGROUND Understanding the changes in energy expenditure and body composition is essential for the optimal management of the critically injured, yet these changes have not been quantified within the current context of trauma care. METHODS Ten critically injured patients (median Injury Severity Score = 35) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and then every 5 days for 21 days. RESULTS Resting energy expenditure rose to 55% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.32 X resting energy expenditure. Body fat was oxidized when energy intake was insufficient (r=-0.830, p<0.02). Body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. Over the 21-day study period, there was a loss of 1.62 kg (16%) of total body protein (p<0.0002), of which 1.09 kg (67%) came from skeletal muscle. Intracellular potassium was low (133 +/- 3 mmol/L, p<0.02) but did not deteriorate further after hemodynamic stability had been reached. CONCLUSIONS These results show that the period of hypermetabolism lasts longer and the protein loss is greater in critically injured patients than previously thought. Most, but not all, the protein is lost from muscle. Fat loss can be prevented and cell composition preserved once hemodynamic stability is achieved.

Components of energy expenditure in patients with severe sepsis and major trauma: a basis for clinical care.

OBJECTIVE To obtain accurate values for the components of energy expenditure in critically ill patients with sepsis or trauma during the first 2 wks after admission to the intensive care unit. DESIGN Prospective study. SETTING Critical care unit and university department of surgery in a single tertiary care center. PATIENTS Twelve severely septic (median Acute Physiology and Chronic Health Evaluation II Score, 23; range, 15 to 34) and 12 major trauma patients (median Injury Severity Score, 33.5; range, 26 to 50). INTERVENTIONS Total body fat, total body protein, and total body glycogen were measured as soon as hemodynamic stability had been reached and repeated 5 and 10 days later. Resting energy expenditure (REE) was measured daily by indirect calorimetry. MEASUREMENTS AND MAIN RESULTS Changes in total body fat, total body protein, and total body glycogen in critically ill patients provide data for the accurate construction of an energy balance. Energy intake minus energy balance gives a direct measurement of total energy expenditure (TEE) and, when combined with measurements of REE, activity energy expenditure can be obtained. TEE, REE, and activity energy expenditure were calculated for two sequential 5-day study periods. REE progressively increased during the first week after the onset of severe sepsis or major trauma, peaking during the second week at 37 +/- 6% (SEM) and 60 +/- 13% greater than predicted, respectively. For both the sepsis and trauma patients, TEE was significantly higher during the second week than during the first week (3257 +/- 370 vs. 1927 +/- 370 kcal/day, p < .05, in sepsis; 4123 +/- 518 vs. 2380 +/- 422 kcal/day, p < .05, in trauma). During the first week after admission to the hospital, TEE in sepsis and trauma patients, respectively, averaged 25 +/- 5 and 31 +/- 6 kcal/kg of body weight/day, and during the second week, 47 +/- 6 and 59 +/- 7 kcal/kg/day (p < .03, for comparison of first and second weeks). For the first week, the ratio of TEE to REE was 1.0 +/- 0.2 and 1.1 +/- 0.2 but during the second week rose to 1.7 +/- 0.2 and 1.8 +/- 0.2 in patients with sepsis (p < .05, for comparison of weeks) and trauma (p = .09), respectively. CONCLUSIONS Total energy expenditure is maximal during the second week after admission to the critical care unit, reaching 50 to 60 kcal/kg/day.

Sequential metabolic changes following induction of systemic inflammatory response in patients with severe sepsis or major blunt trauma.

Abstract. We have recently completed studies in critically ill patients with severe sepsis or major trauma that investigated sequential changes in the metabolic response following admission to the intensive care unit. Protein, water, and energy metabolism were measured using in vivo neutron activation analysis, tracer dilution, dual-energy x-ray absorptiometry, and indirect calorimetry. Over the 3-week study period both groups of patients lost 13% of their total body protein. The severe sepsis patients retained twice the volume of fluid of those with major trauma, and the return to normal hydration in the sepsis group was correspondingly prolonged, especially for those in the elderly age group. In both groups of patients resting energy expenditure increased progressively over the first week to around 40% above normal and was still elevated 3 weeks from onset of illness. A twofold increase in total energy expenditure occurred in both groups of patients between the first and second weeks of critical care admission. The prolonged hypermetabolism throughout the study period was not reflected in the concentrations of circulating proinflammatory cytokines, which fell rapidly over the first week. The pattern of changes seen in plasma proinflammatory and antiinflammatory cytokine concentrations is similar for sepsis and trauma. The remarkably similar metabolic sequelae seen in critically ill patients following the onset of severe sepsis or major trauma may constitute a universal response to the induction of the systemic inflammatory response syndrome.